The proposed research will evaluate the hypothesis that hormonal disturbances brought about by stressful experiences during early development contribute to the individual variability in responsiveness to challenges in the adult organisms. More specifically the proposed research will confine and expand our recent findings of altered sensitivity to ET in adult prenatally stressed offspring compared to those from nonstressed mothers. Subjects for the proposed studies will be male and female rats born to prenatally stressed and control rats. The stressor will be 5 minutes of handling on days 14-21 of gestation. Brain development in rats is not complete at birth, in contrast to man, therefore (for the rodent stress period) to be chronologically equivalent to prenatal stress in man, we will also examine offsprings that will be stressed both pre- and post-natally (daily removal from the cage for 15 minutes from day 1-20). Experiment 1 will examine sensitivity to ET (0,1,3 g/kg IP) of perinatally stressed rats using behavioral (dowel test, swim performance), physiological (rectal temperature) and biochemical (plasma levels of corticosterone, testosterone, NEFA) measures. Blood and brain levels of ET will also be determined. Experiment 2 will determine the specificity of the long term effects of perinatal stress by examining whether similar changes in sensitivity occur in response to other acute challenges (cold, restraint, caffeine, diazepam). Experiment 3 will examine whether changes in adult stress sensitivity are differentially effected by different types of prenatal stressors. Finally Experiments 4 and 5 will explore the functional consequences of the changes in sensitivity to ET. Development of tolerance and severity of the withdrawal syndrome as well as ET preference will be examined in offspring from stressed and non-stressed litters. These studies have significant implications in terms of providing evidence for the basis of individual variability in response to drugs and stressors. Understanding the vasis for individual variability to ET is important because of the implications in cases of legal limits of intoxication. Furthermore by effecting mechanisms involved in the development of TL to ET, prenatal stress may be one of the contributing factors for the development of alcoholism in man
| Pohorecky, L A; Cotler, S; Carbone, J J et al. (1988) Factors modifying the effect of diazepam on plasma corticosterone levels in rats. Life Sci 43:2159-67 |
